Abstracto

Bone marrow stromal-cell line HS-5 affects apoptosis of acute myeloid leukemia cells HL-60 through GLI1 activation

Dongfang Guan, Wenjuan Qing, Cui Ma, Zhiwei Zhang, Hong Wei, Guangsheng Wu

The Hedgehog (HH) pathway regulates cell proliferation and survival and contributes to tumorigenesis. However, not much is known about the role of the HH-signaling system in the bone marrow microenvironment during the development of Acute Myeloid Leukemia (AML). The aim of this study was to investigate the anti-leukemic effects of the HH-signaling pathway and molecular mechanisms of apoptosis induction in AML cells, by blocking the hedgehog signaling pathway during co-culture of AML cells with Bone-Marrow Stromal Cells (BMSCs). It was found that the HS-5 line of BMSCs protected AML cells from spontaneous apoptosis via up-regulation of transcription factors GLI1, BCL-2 and BCL-XL. These results indicate that the up-regulation of the transcription factors involved activation of the hedgehog pathway. Thus, targeting a microenvironment-related signaling pathway may be a novel approach to AML therapy.